Romuald Zdrojowy

Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival

IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02+ subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)+ regulatory T (Treg) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of Treg cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.

The G84E mutation in the HOXB13 gene is associated with an increased risk of prostate cancer in Poland

The G84E mutation in the HOXB13 gene has been associated with a high lifetime risk of prostate cancer in North America (about 20‐fold). The geographical and ethnic extent of this recurrent allele has not yet been determined.

Antegrade endopyelotomy versus laparoscopic pyeloplasty for primary ureteropelvic junction obstruction.

OBJECTIVES A retrospective study was performed to compare the results of laparoscopic pyeloplasty and antegrade endopyelotomy and complications observed after the two procedures. MATERIALS AND METHODS Seventy-five endopyelotomies and 90 laparoscopic pyeloplasties in patients with primary ureteropelvic junction obstruction (UPJO) were performed. The diagnosis of UPJO was based on a complete medical history, ultrasonography, urography (IVU), and/or diuretic renography. In 52 cases, a Whitaker test was performed before endopyelotomy. The mean follow-up was 31 months in the endopyelotomy group and 28.5 months in the laparoscopy group. Complete success was defined as absence of any clinical symptoms combined with significant reduction of hydronephrosis on diuretic IVU and ultrasonography, and no sign of obstruction on diuretic IVU, diuretic renography, or Whitaker test. RESULTS Complete success was observed in 55.4% of patients after endopyelotomy and in 95.3% of patients after laparoscopic pyeloplasty. In patients with primary UPJO, laparoscopic procedures yield better therapeutic results than endopyelotomy, irrespective of the degree of hydronephrosis. The number of complications after the two procedures was comparable with the exception of intraoperative bleeding, which was more frequent in the case of endopyelotomy. CONCLUSIONS Laparoscopic pyeloplasty should be the procedure of choice in the treatment of primary UPJO.

The role of lasers in modern urology

Introduction The functioning of modern urological departments and the high level of service they provide is possible through, among other things, the use of modern laser techniques. Material and methods Open operations have been replaced by minimally invasive procedures, and classical surgical tools by advanced lasers. The search for new applications with lasers began as technology developed. Among many devices available, holmium, diode and thulium lasers are currently the most popular. Results Depending on the wavelength, the absorption by water and hemoglobin and the depth of penetration, lasers can be used for coagulation, vaporization and enucleation. In many centres, after all the possibilities of pharmacological treatment have been exhausted, lasers are used as the primary treatment for patients with benign prostatic hyperplasia, with therapeutic results that are better than those obtained through open or endoscopic operations. The use of lasers in the treatment of urolithiasis, urinary strictures and bladder tumours has made treatment of older patients with multiple comorbidities safe, without further necessity to modify the anticoagulant drug treatment. Laser procedures are additionally less invasive, reduce hospitalization time and enable a shorter bladder catheterization time, sometimes even eliminating the need for bladder catherterization completely. Such procedures are also characterized by more stable outcomes and a lower number of reoperations. Conclusions There are also indications that with the increased competition among laser manufacturers, decreased purchase and maintenance costs, and increased operational safety, laser equipment will become mandatory and indispensable asset in all urology wards.

Evaluation of Bioelectrical Activity of Pelvic Floor Muscles and Synergistic Muscles Depending on Orientation of Pelvis in Menopausal Women with Symptoms of Stress Urinary Incontinence: A Preliminary Observational Study

Objectives. Evaluation of resting and functional bioelectrical activity of the pelvic floor muscles (PFM) and the synergistic muscles, depending on the orientation of the pelvis, in anterior (P1) and posterior (P2) pelvic tilt. Design. Preliminary, prospective observational study. Setting. Department and Clinic of Urology, University Hospital in Wroclaw, Poland. Participants. Thirty-two menopausal and postmenopausal women with stress urinary incontinence were recruited. Based on inclusion and exclusion criteria, sixteen women aged 55 to 70 years were enrolled in the study. Primary Outcome Measures. Evaluation of resting and functional bioelectrical activity of the pelvic floor muscles by electromyography (sEMG) and vaginal probe. Secondary Outcome Measures. Evaluation of activity of the synergistic muscles by sEMG and surface electrodes. Results. No significant differences between orientations P1 and P2 were found in functional and resting sEMG activity of the PFM. During resting and functional PFM activity, higher electrical activity in P2 than in P1 has been recorded in some of the synergistic muscles. Conclusions. This preliminary study does not provide initial evidence that pelvic tilt influences PFM activation. Although different activity of synergistic muscles occurs in various orientations of the pelvic tilt, it does not have to affect the sEMG activity of the PFM.

Comparison of Dismembered and Nondismembered Y-V Laparoscopic Pyeloplasty in Patients with Primary Hydronephrosis

INTRODUCTION A retrospective study was performed to compare the results of dismembered and nondismembered Y-V laparoscopic pyeloplasties and the complications observed after the two types of surgery. MATERIALS AND METHODS Eighty-eight patients with ureteropelvic junction obstruction (UPJO) underwent a laparoscopic operation. In 2 cases, an open conversion was made. A laparoscopic Hynes-Anderson pyeloplasty (LH-AP) was performed on 50 patients, whereas a laparoscopic Y-V pyeloplasty (LY-VP) was performed in 36 cases. The diagnosis of UPJO was based on a complete medical history, ultrasonography, diuretic urography (IVU), and/or diuretic renography. The mean follow-up was 29 (range, 6-66) months. Complete success was defined as the absence of any clinical symptoms, combined with a significant reduction of hydronephrosis on IVU and ultrasonography, as well as no sign of obstruction on IVU and/or diuretic renography. RESULTS The mean operative time for LH-AP was 219 minutes and for LY-VP 185 minutes. The mean hospital stay after LH-AP was 5.9 days and after LY-VP 5.3 days. The overall success rate was 91.5% (91.8% for LH-AP patients and 91.2% for LY-VP patients). CONCLUSION LY-VP appears to be a safe, attractive alternative to LH-AP.

The clinical significance of lymphangiogenesis in renal cell carcinoma

Background The formation of lymphatic vessels (lymphangiogenesis) occurs in tumor tissues and is crucial for tumor development and progression in some cancers. Lymphangiogenesis and its clinical effect on renal cell carcinoma have been less thoroughly investigated in comparison with angiogenesis. The aim of this study was to evaluate the role of lymphangiogenesis as a prognostic factor in renal cell carcinoma (RCC). Material/Methods The expression of peritumoral/intratumoral lymphatics was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 133 patients with clear cell carcinoma. Patients were divided into 3 groups depending on postoperative follow-up: I) patients without metastases, II) patients with metastases during follow-up, and III) patients with metastases during the operation. Peritumoral lymphatics (PTL) and intratumoral lymphatics (ITL) were immunostained with a D2-40 antibody. Results The mean number of PTL present in each group was I=14.1, II=10.6, III=12.1. The mean number of ITL present in each group was I=0.7, II=2.3, III=2.3. The 3 groups showed statistically significant differences only in the case of ITL. A mean count of ITL ≥1 is significantly associated with an increased risk of regional lymph node involvement and distant metastasis. Patients with expression ITL >0.2 and PTL ≤15.2 had a significantly shorter cancer-specific survival. Conclusions The number of ITL showed an association with more aggressive cases of RCC and progression of disease. Therefore, the level of expression ITL, together with stage and histological grading, may provide valuable predictive information about the outcome of treatment.

A common nonsense mutation of the BLM gene and prostate cancer risk and survival

BACKGROUND Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis. Mutations of the BLM gene cause another chromosomal instability clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating mutation of BLM (Q548X) has been associated with a 6-fold increased risk of breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer etiology and survival has not been investigated yet. METHODS To establish whether the Q548X allele of the BLM gene is present in Poland, and whether this allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with prostate cancer and 2604 controls. RESULTS Q548X was detected in 13 of 3337 (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7; 95% CI 0.3-1.4). A positive family history of any cancer in a first- or second-degree relative was seen only in 4 of the 13 (30%) mutation positive families, compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow-up was 49months. Survival was similar among carriers of Q548X and non-carriers (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%, compared to 72% for mutation-negative cases. CONCLUSIONS BLM Q548X is a common founder mutation in Poland. We found no evidence that this mutation predisposes one to prostate cancer or affect prostate cancer survival. However, based on the observed 0.6% population frequency of the Q548X allele, we estimate that one in 100,000 children should be affected by Bloom syndrome in Poland.

Clavien Classification of Complications After 150 Laparoscopic Pyeloplasties

OBJECTIVES To compare the complications of laparoscopic pyeloplasty observed in 3 periods of our learning curve using the Clavien classification. METHODS We reviewed and retrospectively analyzed the records of 150 cases of laparoscopic pyeloplasty performed for primary ureteropelvic junction obstruction at our center. All patients were divided into 3 groups according to the order of the case number (1-50, 51-100, 101-150) to compare the intergroup differences in the preoperative data and perioperative parameters. The postoperative complications were subdivided according to the 5-grade Clavien classification of surgical complications. The groups of patients with and without complications were compared with respect to age, degree of hydronephrosis, positive urine culture before surgery, concomitant nephrolithiasis, crossing vessel, and the type of operation performed (dismembered vs nondismembered). RESULTS The success rate was 90.5%. The mean follow-up was 53.7 months (range 5-103). Intraoperative complications occurred in 9 (6%) of 150 patients and postoperative complications in 27 (18%) of 150 patients. No statistically significant differences were seen between the incidence of intra- and postoperative complications among the compared groups. The only statistically significant difference among the groups with and without complications was the presence of a positive urine culture (19% vs 6%, respectively). CONCLUSIONS The most common complications were connected with stent obstruction, and they did not seem dependent on surgeon experience. Patients with a preoperative positive urine culture might have a greater risk of postoperative complications.

CTLA‐4 and CD28 genes' polymorphisms and renal cell carcinoma susceptibility in the Polish population – a prospective study

Polymorphisms in co-stimulatory genes are associated with susceptibility to several malignances such as breast cancer, cervical cancer and chronic lymphocytic leukemia, but have been scarcely investigated in renal cell cancer (RCC). A total of 310 RCC patients and 518 controls were genotyped for single-nucleotide polymorphisms (SNPs) in the CTLA-4 and CD28 genes: CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*6230G>A (CT60; rs3087243), CTLA-4g.*10223G>T (Jo31; rs11571302), CD28c.17+3T>C (rs3116496) and CD28c.-1042G>A (rs3181098). The distribution of the alleles, genotypes and haplotypes in the CTLA-4 and CD28 genes were similar in the RCC patients and in the controls. However, among the patients with a clear cell RCC (CCRCC), the G allele carriers of CT60 and Jo31 SNPs were overrepresented, and the overrepresentation became significant for the carriers of CT60[G] allele in CCRCC patients with necrosis in the primary tumor (P = 0.046). The CTLA-4c.49A>G[A]/CTLA-4g.319C>T[C]/CT60[A]/Jo31[T]/CD28c.17+3T>C[T]/ CD28c.1042G>A[G] haplotype was associated with an approximately threefold increased risk of primary tumor necrosis in CCRCC patients (P corrected = 0.0000007) and with the advanced stage of disease (IV) (P corrected = 0.001). When stratified by gender, CD28c.-1042G>A[GG] genotype was more frequent in the female CCRCC patients compared with healthy women (P = 0.042). Polymorphisms in the CTLA-4 and CD28 genes, in particular considered together as haplotypes, were associated with increased risk of CCRCC, especially with necrosis and with the advanced stage of disease. The CD28c.-1042G>A SNP modulates the risk of CCRCC in women. These findings indicate that the associations of the CTLA-4 and CD28 polymorphisms with the risk of renal cancer are worth further study in a larger group of patients.